Cargando…

The NRF2-Dependent Transcriptional Regulation of Antioxidant Defense Pathways: Relevance for Cell Type-Specific Vulnerability to Neurodegeneration and Therapeutic Intervention

Oxidative stress has been implicated in the etiology and pathobiology of various neurodegenerative diseases. At baseline, the cells of the nervous system have the capability to regulate the genes for antioxidant defenses by engaging nuclear factor erythroid 2 (NFE2/NRF)-dependent transcriptional mec...

Descripción completa

Detalles Bibliográficos
Autores principales: Boas, Stephanie M., Joyce, Kathlene L., Cowell, Rita M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8772787/
https://www.ncbi.nlm.nih.gov/pubmed/35052512
http://dx.doi.org/10.3390/antiox11010008
_version_ 1784635925643395072
author Boas, Stephanie M.
Joyce, Kathlene L.
Cowell, Rita M.
author_facet Boas, Stephanie M.
Joyce, Kathlene L.
Cowell, Rita M.
author_sort Boas, Stephanie M.
collection PubMed
description Oxidative stress has been implicated in the etiology and pathobiology of various neurodegenerative diseases. At baseline, the cells of the nervous system have the capability to regulate the genes for antioxidant defenses by engaging nuclear factor erythroid 2 (NFE2/NRF)-dependent transcriptional mechanisms, and a number of strategies have been proposed to activate these pathways to promote neuroprotection. Here, we briefly review the biology of the transcription factors of the NFE2/NRF family in the brain and provide evidence for the differential cellular localization of NFE2/NRF family members in the cells of the nervous system. We then discuss these findings in the context of the oxidative stress observed in two neurodegenerative diseases, Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), and present current strategies for activating NFE2/NRF-dependent transcription. Based on the expression of the NFE2/NRF family members in restricted populations of neurons and glia, we propose that, when designing strategies to engage these pathways for neuroprotection, the relative contributions of neuronal and non-neuronal cell types to the overall oxidative state of tissue should be considered, as well as the cell types which have the greatest intrinsic capacity for producing antioxidant enzymes.
format Online
Article
Text
id pubmed-8772787
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-87727872022-01-21 The NRF2-Dependent Transcriptional Regulation of Antioxidant Defense Pathways: Relevance for Cell Type-Specific Vulnerability to Neurodegeneration and Therapeutic Intervention Boas, Stephanie M. Joyce, Kathlene L. Cowell, Rita M. Antioxidants (Basel) Review Oxidative stress has been implicated in the etiology and pathobiology of various neurodegenerative diseases. At baseline, the cells of the nervous system have the capability to regulate the genes for antioxidant defenses by engaging nuclear factor erythroid 2 (NFE2/NRF)-dependent transcriptional mechanisms, and a number of strategies have been proposed to activate these pathways to promote neuroprotection. Here, we briefly review the biology of the transcription factors of the NFE2/NRF family in the brain and provide evidence for the differential cellular localization of NFE2/NRF family members in the cells of the nervous system. We then discuss these findings in the context of the oxidative stress observed in two neurodegenerative diseases, Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), and present current strategies for activating NFE2/NRF-dependent transcription. Based on the expression of the NFE2/NRF family members in restricted populations of neurons and glia, we propose that, when designing strategies to engage these pathways for neuroprotection, the relative contributions of neuronal and non-neuronal cell types to the overall oxidative state of tissue should be considered, as well as the cell types which have the greatest intrinsic capacity for producing antioxidant enzymes. MDPI 2021-12-21 /pmc/articles/PMC8772787/ /pubmed/35052512 http://dx.doi.org/10.3390/antiox11010008 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Boas, Stephanie M.
Joyce, Kathlene L.
Cowell, Rita M.
The NRF2-Dependent Transcriptional Regulation of Antioxidant Defense Pathways: Relevance for Cell Type-Specific Vulnerability to Neurodegeneration and Therapeutic Intervention
title The NRF2-Dependent Transcriptional Regulation of Antioxidant Defense Pathways: Relevance for Cell Type-Specific Vulnerability to Neurodegeneration and Therapeutic Intervention
title_full The NRF2-Dependent Transcriptional Regulation of Antioxidant Defense Pathways: Relevance for Cell Type-Specific Vulnerability to Neurodegeneration and Therapeutic Intervention
title_fullStr The NRF2-Dependent Transcriptional Regulation of Antioxidant Defense Pathways: Relevance for Cell Type-Specific Vulnerability to Neurodegeneration and Therapeutic Intervention
title_full_unstemmed The NRF2-Dependent Transcriptional Regulation of Antioxidant Defense Pathways: Relevance for Cell Type-Specific Vulnerability to Neurodegeneration and Therapeutic Intervention
title_short The NRF2-Dependent Transcriptional Regulation of Antioxidant Defense Pathways: Relevance for Cell Type-Specific Vulnerability to Neurodegeneration and Therapeutic Intervention
title_sort nrf2-dependent transcriptional regulation of antioxidant defense pathways: relevance for cell type-specific vulnerability to neurodegeneration and therapeutic intervention
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8772787/
https://www.ncbi.nlm.nih.gov/pubmed/35052512
http://dx.doi.org/10.3390/antiox11010008
work_keys_str_mv AT boasstephaniem thenrf2dependenttranscriptionalregulationofantioxidantdefensepathwaysrelevanceforcelltypespecificvulnerabilitytoneurodegenerationandtherapeuticintervention
AT joycekathlenel thenrf2dependenttranscriptionalregulationofantioxidantdefensepathwaysrelevanceforcelltypespecificvulnerabilitytoneurodegenerationandtherapeuticintervention
AT cowellritam thenrf2dependenttranscriptionalregulationofantioxidantdefensepathwaysrelevanceforcelltypespecificvulnerabilitytoneurodegenerationandtherapeuticintervention
AT boasstephaniem nrf2dependenttranscriptionalregulationofantioxidantdefensepathwaysrelevanceforcelltypespecificvulnerabilitytoneurodegenerationandtherapeuticintervention
AT joycekathlenel nrf2dependenttranscriptionalregulationofantioxidantdefensepathwaysrelevanceforcelltypespecificvulnerabilitytoneurodegenerationandtherapeuticintervention
AT cowellritam nrf2dependenttranscriptionalregulationofantioxidantdefensepathwaysrelevanceforcelltypespecificvulnerabilitytoneurodegenerationandtherapeuticintervention